As a process for producing a thieno[2,3-d]pyrimidine compound showing the GnRH antagonistic activity, there is a known method for obtaining a thieno[2,3-d]pyrimidine compound by using, as a starting material, 2-amino-4-methyl-5-(4-nitrophenyl)thiophene-3-carboxylic acid ethyl ester which is obtained by reacting 4-nitrophenylacetone with ethyl cyanoacetate, ammonium acetate, acetic acid, sulfur and diethylamine [WO96/24597(JP-A 9-169768)].
In addition, as a process for producing 2-amino-3-ethoxycarbonyl-4-methyl-5-phenylthiophene, there is a known method of acting morphorine or triethylamine on a solution of phenylacetone, ethyl cyanoacetate and sulfur in ethanol (U.S. Pat. No. 4,240,820 etc.).
On the other hand, as a process for producing a methylketone compound, there is a known method of subjecting a magnesium ethoxy derivative of diethyl malonate and a suitable amount of acid chloride to an acylating reaction, which is subjected to a hydrolysis reaction, and subjecting (two ester groups of) the resulting diethyl acylmalonate to a decarboxylation reaction in the presence of an acid (J.Am.Chem.Soc., Vol.68,pp1386(1946)etc.).
In the previous process of production, there are problems that the expensive starting materials are used, high toxic carbon tetrachloride is used, high risky metal magnesium is used, and a compound having the strong skin stimulating property is isolated and, therefore, an industrially advantageous process for producing thieno[2,3-d]pyrimidine derivatives showing the GnRH antagonistic activity is desired.